Current Drug Metabolism - Volume 20, Issue 2, 2019

Background: Cyclosporine A (CsA) is widely used for organ transplantation and autoimmune disorders. However, CsA nephrotoxicity is a serious side effect that limits the clinical use of CsA. The metabolism of CsA has a close relationship with this disease in renal-transplant patients. However, the metabolic pathways of CsA and its metabolizing enzymes have rarely been comprehensively reviewed. In this review, we have summari Read More

Background: Carboxylesterases (CES) play a critical role in catalyzing hydrolysis of esters, amides, carbamates and thioesters, as well as bioconverting prodrugs and soft drugs. The unique tissue distribution of CES enzymes provides great opportunities to design prodrugs or soft drugs for tissue targeting. Marked species differences in CES tissue distribution and catalytic activity are particularly challenging in human tran Read More

Background: Common marmosets (Callithrix jacchus) are potentially useful nonhuman primate models for preclinical studies. Information for major drug-metabolizing cytochrome P450 (P450) enzymes is now available that supports the use of this primate species as an animal model for drug development. Here, we collect and provide an overview of information on the activities of common marmoset hepatic and intestinal mic Read More

Background: Anecdotal evidence suggests that there may be sex differences in Drug-drug Interactions (DDI) involving specific drugs. Regulators have provided general guidance for the inclusion of females in clinical studies. Some clinical studies have reported sex differences in the Pharmacokinetics (PK) of CYP3A4 substrates, suggesting that DDI involving CYP3A4 substrates could potentially show sex differences. O Read More

Background: Recent US Food and Drug Administration (FDA) draft guidance on pharmacokinetic drugdrug interactions (DDIs) has highlighted the clinical importance of ABC transporters B1 or P-glycoprotein (P-gp), hepatic organic anion-transporting polypeptide transporters and breast cancer resistant protein because of their broad substrate specificity and the potential to be involved in DDIs. This guidance has indicated that di Read More

Background: Herbal products have grown steadily across the globe and have increasingly been incorporated into western medicine for healthcare aims, thereby causing potential pharmacokinetic Herb-drug Interactions (HDIs) through the inhibition or induction of drug-metabolizing enzymes and transporters. Human Carboxylesterases 1 (CES1) and 2 (CES2) metabolize endogenous and exogenous chemicals including many i Read More

Background: Due to the special nature of Chinese Herbal medicine and the complexity of its clinical use, it is difficult to identify and evaluate its toxicity and resulting herb induced liver injury (HILI). Methods: First, the database would provide full profile of HILI from the basic ingredients to clinical outcomes by the most advanced algorithms of artificial intelligence, and it is also possible that we can predict possibilities of HILI Read More

Background: Triptolide, a bioactive component in Tripterygium wilfordii extracts, possess strong antiproliferative activity on all 60-National Cancer Institute (NCI) cancer cell lines. However, the widespread use of triptolide in the clinical practice is greatly limited for its multi-organ toxicity and narrow therapeutic window. All the toxic characteristics of triptolide are associated with the pharmacokinetics especially its distribution a Read More

Background: Modern features of drug development such as low permeability, low solubility, and improved release affect the interplay of the gut microbiota and drug metabolism. In recent years, studies have established the impact of plateau hypoxia on gut microbiota, where drug use by plateau populations is affected by hypoxia- induced changes in intestinal microflora-mediated drug metabolism. Methods: In this review, Read More